The role of the IGF system in cancer: from basic to clinical studies and clinical applications

Insulin-like growth factors (IGFs) are important mediators of growth, development, and survival, are synthesized by almost any tissue in the body, and their action is modulated by a complex network of molecules, including binding proteins, proteases and receptors, which all comprise the IGF system. Evidence from in vitro and animal studies suggests that overexpression of IGFs by cancer cells and/or the nearby stroma as well as the type IGF-I receptor by the cancer cells may play a significant role in establishing a transformed phenotype in an increasing number of malignancies. More specifically, IGFs may promote cell cycle progression and inhibition of apoptosis either by directly associating with other growth factors or indirectly by interacting with other molecular systems which have an established role in carcinogenesis and cancer promotion, such as the steroid hormones and integrins. In addition, a growing number of epidemiologic studies suggest that increased serum levels of IGFs and/or altered levels of their binding proteins are associated with increased risk for developing several malignancies. These data indicate that IGF dysregulation should now be considered as an important independent factor for cancer risk, and a potential target for novel antineoplastic therapies and/or preventative strategies in high-risk groups.